Compounds for use as inhibitors of alternative oxidase or cytochrome bc1 complex

Abstract

The invention provides compounds for use in inhibiting a microbial alternative oxidase (AOX) and/or cytochrome bc 1 complex. The invention extends to the use of such inhibitors in agrochemicals and in pharmaceuticals, for treating microbial infections, including fungal infections.

The invention claimed is: 
     
       1. A method of treating a fungal infection in a subject, the method comprising administering to a subject in need of such treatment a therapeutically effective amount of the compound of formula I: 
       
         
           
           
               
               
           
         
         wherein R 1  is a group selected from: CHO; CN; C(O)NH 2 ; C(O)NHCH 3 ; C(O)CH 3 ; COOH; and COOCH 3 ; 
         R 2  is hydrogen, hydroxyl or an alkoxy group with 1 to 3 C atoms; 
         R 3  is a straight chain or branched alkyl or alkylene with 4 to 20 C atoms, that is optionally mono- or polysubstituted by a C 1  to C 4  alkyl group; 
         R 4  is a hydroxyl group; 
         R 5  is a halogen group; and 
         R 6  is H or a C 1  to C 4  alkyl group, 
         wherein the fungal infection is caused by a fungus comprising an alternative oxidase (AOX). 
       
     
     
       2. The method according to  claim 1 , wherein R 2  is a hydroxyl group. 
     
     
       3. The method according to  claim 1 , wherein R 3  is a straight chain or branched alkyl or alkylene with 6 to 15 C atoms, 8 to 12 C atoms or 8 to 10 C atoms, that is optionally mono- or polysubstituted by a C1 to C4 alkyl group. 
     
     
       4. The method according to  claim 1 , wherein R 3  is a diene having 6 to 15 C atoms that is substituted with at least one methyl group. 
     
     
       5. The method according to  claim 1 , wherein R 5  is a chlorine, bromine, fluorine or iodine group. 
     
     
       6. The method according  claim 1 , wherein R 5  is a chlorine group; or wherein R6 is a methyl, ethyl or propyl group. 
     
     
       7. The method according  claim 1 , wherein:
 R 1  is selected from CHO; CN; C(O)NH 2 ; C(O)NHCH 3 ; C(O)CH 3 ; COOH; and COOCH 3 ; 
 R 2  is a hydroxyl group; 
 R 3  is a straight chain or branched alkyl or alkylene with 4 to 20 C atoms, that is optionally mono- or polysubstituted by a C 1  to C 4  alkyl group; 
 R 4  is a hydroxyl group; 
 R 5  is a chlorine atom; and 
 R 6  is H or a C 1  to C 4  alkyl group. 
 
     
     
       8. The method according to  claim 1 , wherein:
 R 1  is selected from CHO; CN; C(O)NH 2 ; C(O)NHCH 3 ; C(O)CH 3 ; COOH; and COOCH 3 ; 
 R 2  is a hydroxyl group; 
 R 3  is a straight chain or branched alkyl or alkylene with 6 to 15 C atoms, that is optionally mono- or polysubstituted by a C 1  to C 2  alkyl group; 
 R 4  is a hydroxyl group; 
 R 5  is a chlorine atom; and 
 R 6  is H or a C 1  to C 4  alkyl group. 
 
     
     
       9. The method according to  claim 1 , wherein:
 R 1  is selected from CHO; CN; C(O)NH 2 ; C(O)NHCH 3 ; C(O)CH 3 ; COOH; and COOCH 3 ; 
 R 2  is a hydroxyl group; 
 R 3  is an alkylene chain having 8 to 10 C atoms, and is substituted with at least one methyl group; 
 R 4  is a hydroxyl group; 
 R 5  is a chlorine atom; and 
 R 6  is a methyl group. 
 
     
     
       10. The method of  claim 1 , wherein the subject is human. 
     
     
       11. The method of  claim 1 , wherein the fungus is selected from a group of genera consisting of  Aspergillus; Blumeria; Candida; Cryptococcus; Encephalitozoon; Fusarium; Leptosphaeria; Magnaporthe; Phytophthora; Plasmopara; Pneumocystis; Pyricularia; Pythium; Puccinia; Rhizoctonia; Trichophyton ; and  Ustilago.    
     
     
       12. The method of  claim 11 , wherein the fungus is selected from a group of species consisting of  Aspergillus flavus; Aspergillus fumigatus; Aspergillus nidulans; Aspergillus niger; Aspergillus parasiticus; Aspergillus terreus; Blumeria graminis; Candida albicans; Candida cruzei; Candida glabrata; Candida parapsilosis; Candida tropicalis; Cryptococcus neoformans; Encephalitozoon cuniculi; Fusarium solani; Leptosphaerianodorum; Magnaporthe grisea; Phytophthora capsici; Phytophthora infestans; Plasmopara viticola; Pneumocystis jiroveci; Puccinia coronata; Puccinia graminis; Pyricularia oryzae; Pythium ultimum; Rhizoctonia solani; Trichophytoninterdigitale; Trichophyton rubrum ; and  Ustilago maydis.    
     
     
       13. The method of  claim 1 , wherein the fungus is  Saccharomyces  spp.,  S. cerevisiae; Candida  spp., or  C. albicans.